It is known that a 7-[4-substituted-3-{(cyclopropylamino)methyl}-1-pyrrolidinyl]q uinolone carboxylic acid derivative not only is safe and has a strong antibacterial activity, but also exhibits a strong antibacterial activity to resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant Enterococcus (VRE) (Patent Literature 1).
An aqueous liquid formulation having a pH that is higher or lower than the physiological pH sometimes provides stimuli when administered. Hence, it is preferable to design an aqueous liquid formulation which has a pH around the physiological pH, that is, a near-neutral pH, when designing an aqueous liquid formulation such as an injectable formulation. Patent Literatures 2 to 7 disclose an aqueous liquid formulation in which a quinolone carboxylic acid derivative is contained as a principal agent and which is neutral pH. These literatures disclose a formulation in which the precipitation of the principal agent is suppressed and the principal agent is solubilized by adding polyvalent metal such as magnesium into a solution (Patent Literatures 2 to 7). Examples of the formulation form include an injectable formulation (Patent Literatures 2 to 5 or 7) and an ophthalmic formulation (Patent Literatures 5 to 7). In any formulation, the principal agent and the polyvalent metal are simultaneously contained in the solution or the suspension, thereby to suppress the precipitation of the principal agent and exert the solubilization effect.
On the other hand, there is known an aqueous liquid formulation in which a solution containing a quinolone carboxylic acid derivative as a principal agent is adjusted to be slightly acidic around pH 4 thereby to improve the chemical and physical stability of the principal agent (Patent Literatures 8 to 9). Patent Literature 9 discloses a formulation which includes a lyophilized formulation containing quinolone carboxylic acid and a dilution liquid containing a polyvalent metal compound.
It is noted that the above-described quinolone carboxylic acid derivative disclosed in Patent Literatures 2 to 9 does not have a cyclopropylaminomethyl structure.